What is the topic?
Hydroxychloroquine (Plaquenil) is in a class of drugs that was originally developed to treat malaria and has been considered to be a safe and effective treatment for mild lupus and rheumatoid arthritis (RA) since 1957. Low blood sugar is an occasional side effect of taking these anti-malarial drugs, but how this happens is not well understood.

What did the researchers hope to learn?
The researchers hoped to learn whether there are any tests that could predict low blood sugar in women with lupus taking hydroxychloroquine.

Who was studied?
161 women with lupus and 185 women with RA with no history of heart disease or diabetes were recruited to the study for a single visit at the University of Pittsburgh. During the visit, each study volunteer provided a blood sample after not eating for 24 hours (which is called “fasting glucose”). Some of the women in each group were taking hydroxychloroquine and some were not.

How was the study conducted?
Blood samples from all of the women were used to study how sugar was being processed in the body. The information was looked at to rule out confusing results that might have been caused by different age ranges, disease duration, waist size, prednisone dose, levels of an inflammatory measure called C-reactive protein, menopausal status, and use of non-steroidal anti-inflammatory drugs. In addition, for the women with lupus, adjustments were made to rule out the influences of immunosuppressant treatments and disease activity.

What did the researchers find?
The women with lupus were significantly younger, more likely to be premenopausal, and more likely to be taking hydroxychloroquine than those with RA. Among women taking hydroxychloroquine, those with lupus were taking a higher dose than those with RA.

For women with lupus, those taking hydroxychloroquine were compared to those who were not taking this treatment. The patients on hydroxychloroquine had lower blood levels of sugar (or fasting glucose) and of a cholesterol carrier called LDL (suggesting less cholesterol in the bloodstream). They also had less insulin resistance (meaning that their insulin was working better at keeping the blood sugar levels normal) than those not taking hydroxychloroquine. They also were more likely to be taking prednisone.

After factoring out all these differences that might be confusing the results in both women with lupus and those with RA, use of hydroxychloroquine was still associated with lower blood sugar (fasting glucose).

What were the limitations of the study?
This study can find associations between blood test results and medication use, but does not prove that this is a cause-effect relationship. There are some factors that could influence the results that were not measured such as “lean body mass” (meaning extra weight) and physical activity levels. The number of patients studied may have been too small to find important differences in some cases, especially in the case of women with RA taking hydroxychloroquine.

What do the results mean for you?
Use of hydroxychloroquine seems to be associated with lower blood sugar and less risk factors for diabetes in women with lupus. This may be a beneficial effect of this safe and inexpensive medication, but studies which show the “before and after” effects of starting this treatment would be needed to determine whether this is actually cause and effect and not a measurement of other differences between those taking the treatment and those not taking the treatment.